Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Affymetrix SNP array data for non-small cell lung cancer cell line samples

ABSTRACT: HCC827 cells were exposed in vitro to the irreversible EGFR inhibitor PF00299804 and resistant clones were isolated. These resistant clones (HCC827 PFR) contained an amplification of the MET gene and the growth of the HCC827 PFR cells was inhibited with the combination of PF00299804 and a MET kinase inhibitor. Phenotypically, these HCC827 PFR cells were similar to our previously identified gefitinib resistant HCC827 (HCC827 GR) cells (Engelman et al. Science 2007). In order to compare global genomic changes between HCC827 GR and HCC827 PFR cells and to determine whether the MET amplicon was similar in both drug resistant cells we performed a genome wide SNP analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18797 | GEO | 2009/10/30

SECONDARY ACCESSION(S): PRJNA121205

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Ito2019 - gefitnib resistance of lung adenocarcinoma caused by MET amplification

Project description:The model is based on publication: Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification Abstract: Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.

2024-09-02 | BIOMD0000000827 | BioModels

Methylation-modulated PFTK1 regulates Gefitinib resistance via Wnt/β-catenin signalling in EGFR mutant non-small-cell lung cancer cells

Project description:We implemented mRNA microarray analysis in HCC827 and Gefitinib resistant cells HCC827/GR to identify differential expression of mRNAs in NSCLC.

2024-12-27 | GSE278453 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of HCC827 and HCC827/GR cells Transcriptomes

Project description:HCC827 cells were obtained from American Type Culture Collection, and the gefitinib resistant HCC827/GR cells were established by gradient dose treatment for parental cells more than 6 months.Our study established an acquired gefitinib-resistant cell line, which exhibited epithelial-mesenchymal transition (EMT) and stem cell-like properties ann transcriptional sequencing and bioinformatics analysis confirmed that.

2022-04-14 | GSE199627 | GEO

Charaterization of genetic alterations and gene expression signatures found in erlotinib-resistant and erlotinib/crizotinib dual-resistant HCC827 subpopulations

Project description:The non-small cell lung cancer (NSCLC) cell line HCC827 harbors an activating EGFR mutation (exon 19 deletion) that confers sensitivity to the FDA-approved EGFR inhibitor erlotinib. By applying the ClonTracer barcoding system, we were able to show the presence of pre-existing sub-populations in HCC827 that contribute to erlotinib resistance. Prior studies implicated that MET amplification confers resistance to erlotinib in this cell line. Therefore we examined the effects of the c-Met inhibitor crizotinib on the barcoded HCC827 population when treated either sequentially or simultaneously with both inhibitors. Despite the significant reduction in barcode complexity, the erlotinib/crizotinib combination treatment failed to eradicate all of the resistant clones implying the presence of an erlotinib/crizotinib dual resistant subpopulation. We performed transcriptome profiling (RNA-seq) to elucidate the potential resistance mechanisms of the dual resistant subpopulation in comparison to vehicle-treated or single agent erlotinib-resistant HCC827 cell populations as controls. mRNA profiling of the subpopulations of human NSCLC cell line HCC827 that contribute to EGFR inhibitor erlotinib and MET inhibitor crizotinib resistance

2014-10-07 | E-GEOD-62118 | biostudies-arrayexpress

Affymetrix SNP array data for non-small cell lung cancer cell line samples, PC-9

Project description:PC-9 cells were exposed in vitro to the reversible EGFR inhibitor ZD1839 (gefitinib) and resistant clones were isolated. One of these resistant clones (PC-9 GR4) was then exposed to the irreversible EGFR inhibitor PF00299804 and dual-resistant clones (PC-9 DRs), or those resistant to both ZD1839 and PF00299804, were isolated. In order to compare global genomic changes between PC-9, PC-9 GR, and PC-9 DR cells, we performed a genome-wide SNP analysis.

2009-12-09 | GSE19388 | GEO

Comparison of receptor tyrosine kinase (RTK) family gene expression between normoxic cells and hypoxia-induced gefitinib resistant clones

Project description:In this study, we explored the mechanisms of hypoxia-induced EGFR TKI resistance in non-small cell lung cancer (NSCLC) harbored activating EGFR mutation. The NSCLC cell lines were exposed to normorxia or 1% oxygen for 4 weeks, and then we tested EGFR TKI sensitivity in normoxic and hypoxic NSCLC cell lines. In this microarray experiment, we used normoxic HCC827 and hypoxia-induced gefitinib resistant clones, C2-3 and C2-10. Those clones were selected with gefitinib treatment after the HCC827 were exposed to 1% oxygen for 4 weeks, and the HCC827 C2-3 and C2-10 clones were selected at random for this study.

2020-12-19 | E-MTAB-9452 | biostudies-arrayexpress

Charaterization of genetic alterations and gene expression signatures found in erlotinib-resistant and erlotinib/crizotinib dual-resistant HCC827 subpopulations

2014-10-07 | GSE62118 | GEO

Resistance to Irreversible EGFR Tyrosine Kinase Inhibitors through a Multistep Mechanism Involving the IGF1R Pathway

Project description:The clinical efficacy of EGFR kinase inhibitors gefitinib and erlotinib is limited by the development of drug resistance. The most common mechanism of drug resistance is the secondary EGFR T790M mutation. Strategies to overcome EGFR T790M mediated drug resistance include the use of mutant selective EGFR inhibitors, including WZ4002, or by the use of high concentrations of irreversible quinazoline EGFR inhibitors such as PF299804. In the current study we develop drug resistant versions of the EGFR mutant PC9 cell line which reproducibly develops EGFR T790M as a mechanism of drug resistance to gefitinib. Neither PF299804 resistant (PFR) or WZ4002 resistant (WZR) clones of PC9 harbor EGFR T790M. Instead, they demonstrate activated IGF1R signaling as a result of loss of expression of IGFBP3 and the IGF1R inhibitor, BMS 536924, restores EGFR inhibitor sensitivity. Intriguingly, prolonged exposure to either PF299804 or WZ4002 results in the emergence of a more drug resistant subclone which contains ERK activation. A MEK inhibitor, CI-1040, partially restores sensitivity to EGFR/IGF1R inhibitor combination. Moreover, an IGF1R or MEK inhibitor used in combination with either PF299804 or WZ4002 completely prevents the emergence of drug resistant clones in this model system. Our studies suggest that more effective means of inhibiting EGFR T790M will prevent the emergence of this common drug resistance mechanism in EGFR mutant NSCLC. However, multiple drug resistance mechanisms can still emerge. Preventing the emergence of drug resistance, by targeting pathways activated in resistant cancers before they emerge, may be a more effective clinical strategy. Total of three samples with duplicate or triplicate each were analyzed.

2012-10-01 | E-GEOD-38404 | biostudies-arrayexpress

Microarray expression profile of long noncoding RNAs in EGFR-TKI resistance of lung adenocarcinoma

Project description:Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, we generate EGFR-TKI-resistant HCC827-8-1 cells to be analyzed by microarray with their parental HCC827cells. gefitinib resistant HCC827-8-1 cells with three replications; gefitinib-sensitive HCC827 cells with three replications

2016-08-23 | E-GEOD-74575 | biostudies-arrayexpress

Activation of IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer

Project description:Previous study has demonstrated that HCC827/gef cells are resistant to gefitinib-induced aspoptosis. To investigate the regulators contributed to gefitinib resistance in lung cancer, we analyzed the gene expression profiles between HCC827 andHCC827/gef cells. Reduced IGFBP7 in TKI-resistant cells reversed resistance to EGFR-TKIs, and increased EGFR-TKI-induced apoptosis through up-regulation of BIM and activation of caspases. Suppression of IGFBP7 attenuated phosphorylation of IGF-IR and downstream AKT in TKI-resistant cells.

2019-02-07 | GSE122005 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data